A systematic review and network meta-analysis of psychological, psychosocial, pharmacological, physical and combined treatments for adults with a new episode of depression

Summary Background Various effective treatments for depression exist. We aimed to identify the most effective first-line treatments for new episodes of less and more severe depression (defined by depression scale cut-off scores), to update NICE guidance on the management of Depression in Adults in England. Methods Systematic review and network meta-analysis of randomised controlled trials (RCTs) published up to June 2020 (PROSPERO registration number CRD42019151328). We analysed interventions by class and individually. The primary efficacy outcome was depressive symptom change (expressed as standardised mean difference [SMD]). The review for this outcome was updated in November 2023. Findings We included 676 RCTs, 105,477 participants and 63 treatment classes. For less severe depression, group cognitive/cognitive behavioural therapy (CT/CBT) class was efficacious versus treatment as usual [TAU], the reference treatment for this population [SMD −1.01 (95% Credible Interval [CrI] −1.76; −0.06)]. For more severe depression, efficacious classes versus pill placebo (reference treatment for this population) included combined individual CT/CBT with antidepressants [−1.18 (−2.07; −0.44)], individual behavioural therapies [−0.86 (−1.65; −0.16)], combined light therapy with antidepressants [−0.86 (−1.59; −0.12)], combined acupuncture with antidepressants [−0.78 (−1.12; −0.44)], individual CT/CBT [−0.78 (−1.42; −0.33)], mirtazapine [−0.35 (−0.48; −0.22)], serotonin and norepinephrine reuptake inhibitors [−0.32 (−0.43; −0.22)], tricyclic antidepressants [−0.29 (−0.50; −0.05)], and selective serotonin reuptake inhibitors [−0.24 (−0.32; −0.16)]. Additional treatments showed evidence of efficacy at the intervention level. Evidence for less and more severe depression was of low and low-to-moderate quality, respectively. In the 2023 update, group yoga and self-help without support emerged as efficacious for less severe depression. For more severe depression, combined group exercise with antidepressants emerged as efficacious, whereas combined light therapy with antidepressants failed to remain efficacious. Interpretation Group CT/CBT (and possibly group yoga and self-help) appears efficacious in less severe depression, whereas antidepressants do not show evidence of effect. Combined antidepressants with individual CT/CBT, acupuncture and, possibly, group exercise, individual psychological therapies (behavioural therapies, CT/CBT) alone, and antidepressants alone appear efficacious in more severe depression. Quality of evidence, cost-effectiveness, applicability and implementation issues also need to be considered when formulating clinical practice recommendations. Funding 10.13039/100010377National Institute for Health and Care Excellence.


Flow diagram of study selection
, 929.*Giosan 2020 data were not included in the NMA due to severe convergence issues caused by the fact that the study compared the same intervention in both arms, but effects were very different between arms, leading to considerable heterogeneity compared with other relevant evidence in the dataset.

Figure 1 :
Figure 1: Flow diagram of study selection for the review update (only new records identified between June 2020 -November 2023 included)

Included and excluded studies identified from the search update Characteristics of included studies, and full references Less severe depression
Kramer, L. V., Gruenzig, S. D.,  Baumeister, H., Ebert, D. D., &

More severe depression Network -treatment class level
update search was eligible for inclusion in the review but its data were not possible to include in the NMA, due to severe convergence issues caused by the fact that the study compared the same intervention in both arms, but effects were very different between arms, leading to considerable heterogeneity compared with other relevant evidence in the dataset.

Risk of bias of new studies included in the NMA (reviewer's judgements) Less severe depression Updated bias-adjusted results: SMDs versus the reference treatment Less severe depression Treatment class level Review update: Bias-adjusted results of the network meta-analysis of standardised mean difference (SMD) of depression scale change scores in adults with a new episode of less severe depression: posterior effects (mean SMD, 95%CrI) of all treatment classes versus treatment as usual (TAU) and treatment class rankings
Treatment classes ordered from best to worst, according to mean ranking.Negative effect values indicate a favourable outcome for treatment classes compared with TAU.Results where 95% CrI do not cross the no effect line are shown in bold.AD: antidepressant; CBT: cognitive behavioural therapy; CrI: credible intervals; CT: cognitive therapy; IPT: interpersonal psychotherapy; PDPT: psychodynamic psychotherapy; SMD: standardised mean difference; SSRIs: selective serotonin uptake inhibitors; TAU: treatment as usual; TCAs: tricyclic antidepressants Negative effect values indicate a favourable outcome for treatment classes and interventions compared with TAU.Results where 95% CrI do not cross the no effect line are shown in bold.CBT: cognitive behavioural therapy; CrI: credible intervals; CT: cognitive therapy; IPT: interpersonal psychotherapy; MBCT: mindfulness-based cognitive therapy; PDPT: psychodynamic psychotherapy; SMD: standardised mean difference; SSRIs: selective serotonin uptake inhibitors; TAU: treatment as usual; TCAs: tricyclic antidepressants